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Multiplication-stimulating activity-induced alkalinization of canine renal proximal tubular cells

Journal Article · · J. Biol. Chem.; (United States)
OSTI ID:7093642
The actions of a variety of polypeptide growth factors on isolated cells are thought to be initiated by stimulation of Na/sup +/-H/sup +/ exchange across the plasma membranes of the cells resulting in intracellular alkalinization. To determine whether insulin-like growth factors (IGFs) exert actions through such a mechanism, the authors incubated suspensions of canine renal proximal tubular segments with insulin or IGF I or with multiplication-stimulating activity (MSA)/IGF II. Changes in intracellular pH were detected by measurements of the distribution of (/sup 14/C)5,5-dimethoxazolidine-2,4-dione. Incubation of segments with 10/sup +9/ M MSA under conditions such that extracellular (Na/sup +/)> intracellular (Na/sup +/) effected intracellular alkalinization detectable within 1-2 min. Alkalinization was not observed under conditions where this gradient was not present. Alkalinization was not prevented by inclusion of 1mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid or 1 mM ouabain in incubations, but was inhibited by amiloride. Incubation of proximal tubular segments with as little as 10/sup +11/ M MSA effected intracellular alkalinization. Incubation with as much as 10/sup -6/ M insulin or IGF I did not. Our findings are consistent with an action of MSA/IGF II to stimulate Na/sup +/-H/sup +/ exchange across the plasma membrane of the renal proximal tubular cell. It is possible that the stimulation represents a mechanism by which actions of IGF II are initiated in growth factor-sensitive cells.
Research Organization:
Washington Univ. School of Medicine, Louis, MO
OSTI ID:
7093642
Journal Information:
J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 261:31; ISSN JBCHA
Country of Publication:
United States
Language:
English